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Kaletra is a co-formulation of two human immunodeficiency virus (HIV) protease inhibitors, lopinavir (LPV) and ritonavir (RTV). LPV is mainly metabolized by cytochome P-450 (CYP) 3A.1,2) On the other hand, RTV inhibits the CYP3A-mediated metabolism of LPV, resulting in higher plasma levels of LPV than when LPV is administered alone, and is followed by a dramatic increase of the area under the plasma concentration versus time curve (AUC). 1,3) Presently in Japan Kaletra is used as a salvage therapy for many HIV-infected patients with multidrug resistance. In spite of the fact that Kaletra was approved for use in December 2000 in Japan, there is no Japanese pharmacokinetic data for the co-administration of LPV with RTV. It is easy to speculate that the pharmacokinetics of LPV co-administered with RTV will be complex since the metabolism of LPV is affected by factors such as concurrent use of antiretroviral compounds, food, body weight, concomitant drug use, etc. [4][5][6] In this report, we tried to evaluate the pharmacokinetic parameters of LPV. Healthy Japanese volunteers were orally administered a single normal dose of Kaletra soft capsules under both fasting and postprandial conditions in order to measure longitudinally the plasma concentrations of LPV and RTV. MATERIALS AND METHODSChemicals LPV, RTV and the internal standard (IS), (5S,8S,10S,11S)-9-hydroxy-2-cyclopropyl-5-(1-methylethyl)-1-[2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid, 5-thiazolylmethyl ester, were generously provided by Abbott Laboratories (Abbott Park, IL, U.S.A.). Ethanol, ethyl acetate, nhexane, acetonitrile and methanol were purchased from Katayama Chemical (Osaka, Japan). Trifluoroacetic acid (TFA) and tetramethylammonium perchlorate were purchased from Tokyo Kasei Kogyo Co., Ltd. (Tokyo, Japan).Study Group Eight healthy Japanese volunteers (2 females and 6 males) aged 28 to 52 years were enrolled in the study (Table 1). None of the subjects were excessively overweight/obese or lean. All volunteers participated in the fasting study and seven of them participated in the postprandial study. Written informed consent was obtained from all volunteers.Study Design Three Kaletra soft capsules (400 mg LPV/ 100 mg RTV) were administered to volunteers under fasting or postprandial conditions. In the fasting study, the volunteers fasted for at least 12 h before drug administration. The meal for the postprandial study contained approximately 530 kcal and 20 g of lipid. The volunteers consumed the meal in the morning and took the drug 30 min after they finished eating. Blood samples were obtained at 1, 2, 3, 4, 6, 8, 12, 18, 24 and 30 h after drug administration. The blood samples were centrifuged at 2800ϫg for 5 min to separate the plasma. The pharmacokinetic parameters of lopinavir (LPV) were examined by administering Kaletra (LPV؉riton-avir) to 8 healthy Japanese volunteers both in the fasting and postprandial conditions. LPV showed a biphasic decline, which was slower in the initial phase ...